The long-term objectives of this project are to arrive at an understanding of how the nervous system generates behavior and how its neuronal components and circuitry arise during ontogeny. To this end, we are studying the structure, function and development of the nervous system of leeches. The research plan proposed in this application concerns the development of the nervous system in embryos of the neurologically and embryologically highly favorable leeches Haementeria ghilianii, Helobdella triserialis and Theromyzon rude. Although leeches are phyletically remote from mammals, it can be expected that this project will provide insights of general relevance for understanding developmental mechanisms, including those governing normal and abnormal human development. Our specific aim is to identify the elements of the metameric mesodermal cell clone descended from each primary m blast cell that are necessary for laterad migration of neuroblasts within the ganglionic rudiment and that provide topographic cues for the orthotopic placement of neuroblasts and axon outgrowth in ganglion morphogenesis. Although circular and longitudinal muscle fibers are prime candidates for the elements of the mesodermal cell clone that guide neuroblast migration, the mesodermal tissues in contact with the ganglionic rudiment will be examined for the presence of other cell types which might perform that morphogenetic function. Various partial disruptions of the normal mesodermal cell pattern or function will be produced and these disruptions will be correlated with the resulting abnormalities of neuronal positioning or axonal projection patterns. Embryos will be exposed to oligopeptides known to interfere with binding of fibronectin-like adhesion proteins in order to interfere with migration of neuroblasts by inhibition of their adhesion to the substrate provided by mesodermal cell types.